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Pseudoprogression and radiation necrosis prevent confident interpretation of magnetic resonance imaging (MRI) results and lead to challenges in the management of glioblastoma (GBM). We examined the utility of matrix metalloproteinase-2 (MMP-2) and neutrophil gelatinase-associated lipocalin (NGAL) in the serum and urine as biomarkers of tumor burden in patients with GBM, with the goal of improving the interpretation of MRI and predicting overall survival (OS) and progression free survival (PFS). Expression of MMP-2 and NGAL was analyzed by immunohistochemistry in GBM and non-tumor epileptic control tissues. Serum and urine samples were collected pre and postoperatively and at each MRI. MMP-2 and NGAL levels in the serum and urine were measured by enzyme-linked immunosorbent assay.  MRI results, tumor volumes, survival, symptoms, and quality of life were assessed using repeated measures and autoregressive models correlation structure. Although the staining intensity of NGAL was indistinguishable, GBM tissues exhibited significantly higher number of NGAL positive cells as compared to control epileptic brain tissue. Serum MMP-2 was significantly higher in GBM patients than control subjects (p=0.0112) and was highest in patients who underwent biopsy compared to maximal resection (p=0.0038). Elevated levels of both NGAL and MMP-2 in the preoperative samples indicated a trend towards shorter PFS and OS, while preoperative urine NGAL levels were marginally predictive of PFS. Trajectory of symptoms and quality of life results were too variable to adequately correlate with the biomarker levels. Although biomarkers did not aid in differentiating between pseudoprogression, radiation necrosis, and tumor growth, preoperative levels correlated with survival.